Role of luminal H+ in the pathogenesis of experimental esophagitis.
The pathogenesis of acidic reflux esophagitis was investigated in an experimental model with special emphasis on the role of lumen-to-mucus diffusion of H+ in the pathogenetic mechanism. Esophageal damage was produced by perfusing an isolated segment of rabbit esophagus in situ with three injurious endogenous secretions of the upper gastrointestinal tract (taurocholate, 10 mM; pepsin, 2500 U/ml; lysolecithin, 2 mg/ml) with and without acid (HCl, 10 to 150 mM). The severity of mucosal damage was assessed using as indicators of mucosal integrity transmucosal potential difference, net flux of Na+, and mucosal permeability to two neutral molecules of different sizes--3H-H2O and 14C-erythritol. The data indicate that although the presence of luminal acid is needed for mucosal damage to develop, there is no relationship between the severity of the damage and the magnitude of the lumen-to-mucosa diffusion of H+. Even markedly increased diffusion of H+ alone, induced by an unphysiological high concentration of luminal acid (300 mM HCl), had only a minor influence on mucosal integrity, whereas all three test agents were able to cause severe mucosal damage in association with much lower rates of H+ diffusion. Furthermore, the severity of the mucosal damage caused by an individual test agent was not dependent on the HCl; concentration used (and hence on the magnitude of lumen-to-mucosa diffusion of H+). The data suggest that esophageal mucosal damage caused by taurocholate, pepsin, or lysolecithin in the presence of luminal acid is due to the direct action of the agent itself rather than to excessive accumulation of luminal H+ into the mucosal tissue.
D000818:Animals; D004942:Esophagitis, Peptic / Q000503:physiopathology*; D004947:Esophagus / Q000503:physiopathology; D005750:Gastric Juice / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008244:Lysophosphatidylcholines / Q000502:physiology; D009092:Mucous Membrane / Q000503:physiopathology; D010434:Pepsin A / Q000502:physiology; D011817:Rabbits; D013656:Taurocholic Acid / Q000502:physiology
D008244:Lysophosphatidylcholines; D013656:Taurocholic Acid; D010434:Pepsin A